Discussion
Syphilitic orchitis is a rare manifestation of gummas in patients with tertiary syphilis. Syphilitic gummas may present as a testicular mass and mimic malignant neoplasms clinically. Until recently, fewer than 20 cases had been reported in the English literature [
3].
Microscopic features of syphilitic gummas, which are characterized by granulomatous inflammation with central necrosis and peripheral fibrosis, belong to the spectrum of granulomatous orchitis. In our case, the gross and microscopic findings were atypical for syphilitic gummas, but rather nonspecific interstitial infiltration of lymphoplasma cells, histiocytes, and foamy histiocytes, associated with microabscesses and spindle cell proliferation. A number of etiologies and morphological simulating entities should be considered in the differential diagnosis.
Malakoplakia usually occurs in patients with immunosuppression or a history of a prior urinary tract infection. The histological features are characterized by dense epithelioid histiocyte infiltration in the seminiferous tubules and interstitium. Histiocytes have foamy and eosinophilic granular cytoplasm, termed von Hansemann histiocytes. Some of the histiocytes contain basophilic, laminated, and mineralized concretions in the cytoplasm, so-called Michaelis-Gutmann bodies, which can be highlighted by periodic acid-Schiff, von Kossa, and iron stains [
4,
5]. The specialized von Hansemann histiocytes and Michaelis-Gutmann bodies were not found in the current case.
Rosai-Dorfman disease rarely involves the testes, and may be clinically confused with neoplasms. Microscopically, characteristic histiocytes with centrally placed nuclei, small nucleoli, and abundant pale eosinophilic cytoplasm infiltrating in the testicular interstitium are seen. The diagnostic feature is emperipolesis with lymphocytes in the cytoplasm of the histiocytes. Immunohistochemically, the histiocytes are diffusely positive for S-100 and CD68, but negative for CD1a [
5,
6]. Although considerable numbers of histiocytes were noted in this case, emperipolesis could not be identified.
IgG4-related sclerosing disease is a fibroinflammatory tumorous lesion involving multiple sites. The histological features include dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. In an IHC study, there are increased IgG4 positive plasma cells (>10 per 10 high power field). This multiorgan disease may involve the genitourinary tract, but testicular or paratesticular involvement is rare [
7]. In this case, no significant IgG4-positive plasma cell infiltration was seen.
In addition to a background of dense mixed inflammatory cell infiltration, spindle cell proliferation was also seen in our case. Thus, a panel of spindle cell tumors in an inflammatory background should be considered in the differential diagnosis. Inflammatory myofibroblastic tumors, rarely seen in the testes, are characterized by proliferation of spindle fibroblastic-myofibroblastic cells in a fascicular pattern, admixed with inflammatory cells, including lymphocytes, plasma cells, and eosinophils, infiltrating in a myxoid or collagenous stroma [
8]. Immunohistochemically, the spindle tumor cells show variable staining for smooth muscle actin, desmin, and ALK. In this case, the spindle cell area revealed positivity of smooth muscle actin, suggesting a myofibroblastic nature. ALK positivity occurs in about 50% of cases of inflammatory myofibroblastic tumors [
8]. Although ALK immunoreactivity was negative in this case, the possibility of an inflammatory myofibroblastic tumor could not completely be excluded.
Follicular dendritic cell sarcomas are also composed of ovoid to spindle tumor cells with vesicular nuclei, small nucleoli, palely eosinophilic cytoplasm, and indistinct cell border arranged in fascicular and storiform patterns. The background shows prominent admixed lymphocytes [
9]. Immunohistochemically, tumor cells express dendritic cell markers, including CD21, CD23, and CD35, which were negative in the spindle cell population in the present case.
Interdigitating dendritic cell sarcomas, exceeding rare tumors that share similar histological features with follicular dendritic cell sarcomas, were reported in the testes [
10]. Immunohistochemically, this sarcoma expresses S-100, CD1a, and vimentin, but is consistently negative for follicular dendritic cell markers. In this case, no S-100 or CD1a immunoreactivity was detected in the spindle cells.
Conclusion
Syphilitic gummas, a granulomatous type of tertiary syphilis, can clinically mimic testicular tumors. The histological differential diagnosis includes granulomatous orchitis of various etiologies. Syphilitic orchitis of the nongranulomatous type, as in the current case, features a nonspecific inflammatory reaction and spindle cell proliferation; the differential diagnosis extends to a spectrum of spindle cell tumors intermingled with dense infiltration of inflammatory cells. In such difficult diagnostic cases, a panel of histochemical and IHC studies, with the aid of clinical information and laboratory tests, can achieve a correct diagnosis. Especially in HIV-positive patients, serum VDRL and RPR tests may show false-negative results, as in this case. PCR testing for the T. pallidum DNA polymerase I gene using paraffin-embedded tissue is a sensitive and specific method for diagnosing syphilitic orchitis. From this case, both clinicians and pathologists can learn that syphilitic orchitis should be one of the differential diagnoses in an immunocompromised patient with a testicular tumor, even in the absence of gummatous granulomatous inflammation.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CYC participated in drafting the manuscript and reviewing the literature. CLF and WYC were responsible for making the pathologic diagnosis. SDY provided clinical information of the patient. HMY was responsible for making the radiological diagnosis. CLF proposed the idea and revised the manuscript. All authors have read and approved the final manuscript.